The long-term goal of this project is to identify molecular mechanisms that regulate the stability and plasticity of dendritic spines, small postsynaptic structures that play key roles in signal processing in neuronal circuits. Disruptions of spine numbers and shape occur in many neurological and neuropsychiatric diseases, including mood disorders, autism, and neurodegenerative disease. The size and shape of spines correlates with the physiological strength of the synapse, thus understanding the key molecular pathways that regulate spine shape and stability are crucial for designing therapies to combat such cognitive diseases. This project will focus on a central molecular pathway controlling spine shape and stability that involves the protein MARCKS. Using quantitative fluorescence imaging in dissociated cultures of rodent neurons, the project will characterize the function of MARCKS in dendritic spines using cellular and molecular approaches. Project objectives are to identify the interaction of MARCKS with downstream effectors and their influence on actin filaments and synaptic protein assemblies. PUBLIC HEALTH RELEVANCE: The long-term goal of this project is to identify molecular mechanisms that regulate the stability and plasticity of dendritic spines, small postsynaptic structures that play key roles in signal processing in neuronal circuits. Disruptions of spine numbers and shape occur in many neurological and neuropsychiatric diseases, including mood disorders, autism, stroke, and neurodegenerative disease. The size and shape of spines correlates with the physiological strength of the synapse, thus understanding the key molecular pathways that regulate spine shape and stability are crucial for designing therapies to combat such cognitive diseases. This project will focus on a central molecular pathway controlling spine shape and stability that involves the protein MARCKS and the signaling phospholipid PIP2. Using quantitative fluorescence imaging in dissociated cultures of rodent neurons, the project will characterize the function of MARCKS in dendritic spines using cellular and molecular approaches. Project objectives are to identify the interaction of MARCKS with downstream effectors and their influence on actin filaments and synaptic protein assemblies.